(A) According to a widely held model, the hippocampus temporarily stores new memories and transfers them gradually to the neocortex. Hasselmo (1999) reviews evidence that feedback pathways within the hippocampal CA3 region and from CA3 to CA1 and further to the neocortex are inhibited during wakefulness and REM sleep by acetylcholine (ACh). During SWS, these synapses become disinhibited because of the low cholinergic tone, and information can flow back to the neocortex. (B) Undisturbed SWS features low levels of ACh (left, empty bar). When during SWS-rich sleep cholinergic tone is increased by infusion of the cholinesterase inhibitor physostigmine (left, empty bar), the sleep-related memory benefit is abolished for hippocampus-dependent, declarative wordlist memory (***P < 0.001). During wakefulness, which is accompanied by already high levels of ACh, physostigmine has no such effect (right, filled bar). Modified with permission from Elsevier © 1999, Hasselmo 1999, and with permission from The National Academy of Sciences of the United States of America © 2004, Gais and Born 2004.